Association between triallelic polymorphism of the serotonin transporter and [18F]MPPF binding potential at 5-HT1A receptors in healthy subjects.

Abstract Previous [ 11 C]WAY100-635 PET studies have demonstrated that the short (S) and long (L) alleles of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) were associated with distinct patterns of 5-HT 1A receptor distribution in human. However, these studies reported discordant findings and did not take into account the recent description of two functional variants of the L allele (L A /L G ). To further explore this issue, we investigated the triallelic functional polymorphism of the 5-HTTLPR in 38 healthy volunteers who underwent a [ 18 F]MPPF PET study of 5-HT1A receptors. We used a simplified reference tissue model to generate parametric images of [ 18 F]MPPF binding potential (BP ND ), and compared these data among the different genotypes using statistical parametric mapping and region of interest of the raphe nuclei. Homozygote carriers of the S allele demonstrated greater [ 18 F]MPPF BP ND than carriers of the L A allele, but this association was only found in women. Differences in [ 18 F]MPPF BP ND between women with and without L A allele were observed over large clusters encompassing the right and left temporal lobes, cingulate and perisylvian regions, as well as the right precuneus and frontal dorso-lateral cortex, and the left orbitofrontal cortex. In contrast, no difference was found between groups in the raphe nuclei. The greater [ 18 F]MPPF BP ND observed in women homozygote carriers of the S allele could either reflect a greater 5-HT1A receptor density or a lower extracellular concentration of 5-HT. Our data suggest that any future PET studies of 5-HT1A receptors should incorporate the 5-HTTLPR polymorphism status of the population studied.